A new era in the detection of urothelial carcinoma by sequencing cell-free DNA

摘要

Bladder cancer is a common malignancy with approximately 430,000 new cases diagnosed and 165,000 deaths recorded globally in 2012 ( ). Histologically, 90% of bladder cancers originate from the urothelium. Urothelial bladder carcinoma (UBC) is the most common malignancy of the urinary tract. Approximately 25% of UBCs are classified as muscle-invasive bladder cancer (MIBC), which usually requires radical cystectomy, lymph node dissection, and/or perioperative platinum-based chemotherapy. Despite aggressive therapy, a certain number of MIBC patients will experience disease recurrence and die of cancer. Patients with pT2 tumors have relatively good 5-year disease specific survival (DSS), ranging from 70% to 81%. However, patients with ≥ pT3 tumors have a significantly worse prognosis, with 5-year DSS ranging from 40% to 52% ( - ). Pathological node-positivity is also associated with a poor prognosis, with 5-year DSS ranging from 21% to 35% ( , ). For locally advanced MIBC, neoadjuvant platinum-based chemotherapy has been used to improve these unsatisfactory outcomes since the 1980s. Several randomized controlled trials have been performed to define the usefulness of neoadjuvant chemotherapy ( , ); however, platinum-based chemotherapy in the neoadjuvant setting for patients with locally advanced MIBC is still associated with several issues. First, CT or MRI often result in the overdiagnosis or underdiagnosis, with a staging accuracy of only 70% in clinical setting ( ). Thus, it is difficult for physicians to evaluate the response to systemic chemotherapy based on radiographic imaging alone. Second, neoadjuvant chemotherapy could delay radical cystectomy in patients who do not respond to chemotherapy and thus experience cancer progression during chemotherapy. A reliable biomarker is necessary for physicians to decide whether to perform neoadjuvant chemotherapy, whether to start immune checkpoint inhibitor, and when to perform radical surgery. There have been several studies about biomarkers to detect disease recurrence, to monitor the efficacy of systemic chemotherapy, or to predict drug response ( - ); however, few biomarkers have shown potential, and there is insufficient evidence to support their routine clinical use.